Optimal frequency of lithium administration in the treatment of bipolar disorder: clinical and dosing considerations

Bipolar disorder is a recurrent chronic illness distinguished by periods of mania and depression. Lithium has been used for about 60 years as a 'mood stabilizer' for bipolar disorder with proven efficacy in preventing relapse of both mania and depression. Despite its long history and ongoing use in current management of bipolar disorder, the optimal dosing of lithium is still the subject of ongoing debate. This article aims to evaluate different dosing schedules, in the light of the unique pharmacokinetic and pharmacodynamic properties of lithium, as well as its adverse-effect and toxicity profiles. This is all the more important given the narrow therapeutic index of lithium. Current recommendations mostly advocate that lithium be administered in multiple daily doses. However, single daily or alternate daily schedules may be viable options for administration. Multiple daily schedules are thought to be advantageous in maintaining more constant plasma lithium concentrations than single daily regimens, which are associated with significant fluctuations throughout the day. When comparing these two schedules with respect to plasma lithium concentrations, adverse-effect profiles and recurrence of symptoms, there are no significant differences between the two regimens. In fact, a single daily regimen may have added advantages in reducing the risk of long-term renal damage and increasing compliance. The evidence for alternate daily dosing is somewhat varied with regard to symptom recurrence; however, this schedule has been shown to be associated with decreased adverse effects, and further research into this issue is therefore warranted. Presently, therefore, clinicians should consider single daily administration of lithium to potentially minimize adverse effects and enhance compliance.